The LMIV's mission is to address the global need for a malaria vaccine by focusing fundamental and clinical research in malaria immunobiology and vaccinology. The significance of such effort cannot be overstated, given the morbidity and mortality associated with this disease. While recognition of the impact of malaria on the health and economic stability of much of the world's population has been slow to develop, the attention given to this disease by the NIH, private philanthropists, and the WHO has generated support and momentum for this initiative. The LMIV is collaborating with a number of investigators within the US and throughout the world to contribute to this effort, as well as with the extramural NIH malaria program and with a variety of funding agencies such as USAID and the Gates Malaria Vaccine Initiative. We intend to develop vaccine candidates and test them first in the US and later in malaria-endemic areas. The latter will be done in close collaboration with colleagues in Mali, which will build vaccine testing capacity in this country. An asexual blood-stage vaccine will elicit immune responses capable of either destroying malaria parasites in the blood stream or inhibiting parasites from infecting red blood cells. In either case, the net effect is to reduce or prevent burden of parasites and hence decrease the incidence, severity, or the complications of disease. Such a vaccine would target blood-stage parasite proteins since these antigens are abundantly expressed by parasites during persistent infections. It would act to prime the immune system for subsequent infection in infants or it would boost already present, yet weak, natural immunity in young children. Furthermore, a vaccine composed of multiple antigens will increase the number of individuals responding to at least one component of the vaccine. The inclusion of multiple alleles of polymorphic proteins would also minimize immune pressure on parasite selection, thus decreasing the likelihood of parasite breakthrough.